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Drug discovery

Rules were made to be broken

Twenty five years ago, Christopher Lipinski and colleagues published arguably the most influential sentence in small-molecule drug discovery. Their cleverly crafted ‘rule of 5’ (Ro5) mnemonic was adopted into everyday medicinal chemistry practice and has influenced a generation of small-molecule drug discovery scientists. Five times five years later, we consider the impact of the Ro5 and ask to what extent it should still guide today’s medicinal chemistry efforts.

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Correspondence to Ingo V. Hartung.

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Competing interests

I.V.H. is an employee of Merck Healthcare KGaA. B.R.H. and A.C. are employees of EMD Serono, Inc.

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Hartung, I.V., Huck, B.R. & Crespo, A. Rules were made to be broken. Nat Rev Chem 7, 3–4 (2023).

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